HER2/neu oncogene-mediated malignancy is clearly associated with various human cancers.
Therefore, HER2/neu targeting is an effective approach to cancer therapy. We have
previously demonstrated that Epstein–Barr virus nuclear antigen-1 (EBNA1) can suppress
HER2/neu oncogene expression, although EBNA1 itself has oncogenic potential. Here, we
found that the N-terminal domain of EBNA1 alone, named EBNA1-NT, which contains
the N-terminal region of amino acid residues 1–86 of EBNA1, is required and sufficient
to suppress HER2/neu oncogene expression at the transcriptional level. Furthermore, in
EBNA1-NT-transfected HER2/neu-overexpressing cells, we found EBNA1-NT could downregulate
the endogenous production of p185HER2/neu, lower transformation ability, sensitize
paclitaxel-induced apoptosis and decrease tumorigenic potential. These data suggest that
EBNA1-NT may act as a repressor of the HER2/neu oncogene.
